formin homology protein mDia1 is a Rho GTPase effector protein, which appears to be universally present in eukaryotic cells and participates in: Stress fiber formation Endocytosis Microtubule functions Stress fibers are acto-myosin structures, which are important for establishment of cellular tension and thus traction to move a cell ahead; the later is mediated via cell adhesions. Stress fibers are bundles of about 20 actin filaments linked via non-muscle myosin II. In vitro studies showed that mDia1 assembled stress fibers downstream of Rho. Live-cell imaging analysis revealed that mDia1 indeed assembles stress fibers, which are connected at one of their ends to focal adhesions, where actin polymerization occurs. Stress fiber assembly at focal adhesions by mDia1 was later shown to promote their growth and stabilization, suggesting mDia1 exerts effects on the interactions of cells with their environment. Formins regulate endocytosis. mDia 1 localizes to endosomes and regulates phagocytic cup formation in macrophages. mDia1 (and mDia2) seems to stabilize microtubules by decreasing the tubulin subunit exchange at their plus ends. The exact mechanism is not fully understood yet. However, the affinity of formins for actin are much higher than for microtubules. By catalyzing actin polymerization and stabilizing microtubules, mDia1 plays also an important role for cell migration. Discovery mDia1 was discovered as p140mDia1 by Watanabe et al. in 1997 as a downstream effector of Rho. A mouse embryo cDNA library was screened to identify a RhoA-GTP-binding protein using a yeast two-hybrid system. Further it was shown that p140mDia1 binds to the GTP-bound form of RhoA only by precipitation from Swiss 3T3 cell lysates. Watanabe et al. could also show the interaction of p140mDia1 with profilin and the colocalization of RhoA, p140mDia and profilin in membrane ruffles of motile cells. A subsequent study in 1997 by Bione et al. established a link between human DIA and oogenesis, with a defect in the gene leading to premature ovarian failure. See also DIAPH1 References External links Protein Database Cell cycle Genes mutated in mice Mouse proteins